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70.507 61.973 l
70.544 62.011 l
70.562 62.011 70.581 62.066 70.581 62.102 c
70.581 62.14 70.598 62.195 70.598 62.231 c
70.598 62.268 70.617 62.342 70.617 62.378 c
70.617 62.416 70.617 62.471 70.617 62.526 c
70.617 62.6 70.617 62.655 y
70.636 62.674 l
h
72.309 63.078 m
72.309 63.115 72.29 63.17 72.272 63.17 c
72.236 63.206 72.198 63.206 v
72.162 63.225 72.126 63.261 72.126 63.299 c
72.126 63.318 l
72.126 63.39 72.217 63.447 72.364 63.447 c
73.082 63.447 l
73.191 63.447 73.32 63.428 73.413 63.409 c
73.523 63.373 73.614 63.318 73.687 63.261 c
73.761 63.206 73.835 63.115 73.871 63.023 c
73.909 62.913 73.945 62.784 73.945 62.636 c
73.945 62.617 l
73.945 62.507 73.928 62.397 73.909 62.323 c
73.89 62.25 73.835 62.158 73.799 62.102 c
73.706 61.992 73.578 61.882 73.449 61.844 c
73.394 61.827 73.32 61.808 73.284 61.808 c
73.227 61.808 73.155 61.789 73.118 61.789 c
72.841 61.789 l
72.824 61.789 72.786 61.789 72.75 61.789 c
72.713 61.789 72.677 61.789 y
72.345 61.789 l
72.327 61.789 72.29 61.789 y
72.272 61.789 l
72.236 61.789 72.181 61.808 72.143 61.808 c
72.107 61.827 72.088 61.863 72.088 61.901 c
72.088 61.918 l
72.088 61.956 72.107 61.992 72.143 61.992 c
72.181 62.011 72.236 62.047 72.254 62.066 c
72.272 62.066 72.29 62.14 72.29 62.25 c
72.309 63.078 l
h
73.027 63.189 m
72.934 63.189 l
72.898 63.189 72.879 63.17 72.879 63.151 c
72.879 63.133 72.86 63.078 72.86 63.041 c
72.86 62.14 l
72.86 62.066 72.898 62.011 72.953 62.011 c
72.989 62.03 73.008 62.03 v
73.044 62.03 73.082 62.047 73.099 62.047 c
73.136 62.047 73.173 62.085 73.191 62.121 c
73.227 62.176 73.284 62.268 73.32 62.342 c
73.339 62.433 73.356 62.545 73.356 62.636 c
73.356 62.765 73.32 62.894 73.284 62.986 c
73.227 63.096 73.118 63.17 73.008 63.17 c
73.027 63.189 l
h
74.24 62.691 m
74.24 62.839 74.221 62.949 74.221 63.023 c
74.221 63.06 74.185 63.096 74.185 63.115 c
74.166 63.133 l
74.128 63.151 l
74.092 63.189 74.074 63.206 v
74.056 63.206 74.037 63.244 74.037 63.261 c
74.037 63.318 74.092 63.373 74.185 63.39 c
74.276 63.428 74.405 63.447 74.533 63.447 c
74.607 63.447 74.681 63.447 74.717 63.447 c
74.755 63.447 74.81 63.409 74.846 63.409 c
74.92 63.39 74.974 63.335 74.974 63.299 c
74.974 63.261 l
74.974 63.244 74.957 63.206 y
74.938 63.206 74.901 63.17 74.883 63.17 c
74.828 63.151 74.791 63.06 74.791 62.931 c
74.791 62.526 l
74.791 62.507 74.791 62.471 74.791 62.452 c
74.791 62.416 74.791 62.378 74.791 62.36 c
74.791 62.305 74.791 62.231 74.791 62.195 c
74.791 62.158 74.81 62.102 y
74.81 62.085 74.846 62.047 74.883 62.047 c
74.901 62.047 74.92 62.03 y
74.957 61.992 l
74.974 61.956 74.974 61.937 v
74.974 61.918 l
74.974 61.863 74.901 61.808 74.828 61.789 c
74.791 61.789 74.736 61.789 74.7 61.789 c
74.643 61.789 74.571 61.772 74.515 61.772 c
74.479 61.772 l
74.35 61.772 74.24 61.789 74.185 61.789 c
74.111 61.808 74.074 61.863 74.074 61.901 c
74.074 61.918 l
74.074 61.956 74.092 61.992 74.128 62.011 c
74.166 62.03 74.202 62.066 74.202 62.085 c
74.221 62.121 74.24 62.25 74.24 62.397 c
74.24 62.691 l
h
75.086 62.6 m
75.067 62.6 l
75.067 62.746 75.122 62.894 75.196 63.023 c
75.27 63.133 75.398 63.244 75.527 63.318 c
75.673 63.39 75.839 63.447 75.987 63.447 c
76.023 63.447 76.116 63.428 76.207 63.39 c
76.299 63.354 76.373 63.335 76.409 63.335 c
76.445 63.335 l
76.502 63.354 l
76.538 63.354 76.574 63.335 76.612 63.299 c
76.63 63.261 76.667 63.206 76.685 63.151 c
76.703 63.078 76.721 63.004 76.721 62.968 c
76.721 62.82 76.648 62.71 76.538 62.71 c
76.502 62.691 l
76.483 62.691 76.445 62.71 76.428 62.729 c
76.409 62.729 76.373 62.765 y
76.354 62.803 l
76.335 62.803 76.316 62.839 76.316 62.858 c
76.299 62.875 76.262 62.913 y
76.244 62.949 76.188 63.004 76.152 63.041 c
76.097 63.078 76.004 63.115 75.93 63.115 c
75.894 63.115 75.858 63.096 75.839 63.096 c
75.802 63.078 75.747 63.023 75.729 62.986 c
75.692 62.949 75.673 62.875 75.673 62.803 c
75.673 62.746 75.692 62.674 75.692 62.617 c
75.711 62.562 75.747 62.488 75.766 62.433 c
75.802 62.36 75.875 62.287 75.949 62.25 c
75.987 62.25 76.023 62.213 76.059 62.213 c
76.097 62.213 76.171 62.195 76.207 62.195 c
76.262 62.195 76.335 62.213 76.373 62.213 c
76.409 62.231 76.464 62.268 76.502 62.305 c
76.538 62.323 76.574 62.342 76.593 62.342 c
76.612 62.342 76.648 62.323 76.667 62.305 c
76.667 62.287 76.685 62.25 76.685 62.231 c
76.685 62.121 76.63 62.03 76.538 61.956 c
76.464 61.901 76.354 61.844 76.244 61.827 c
76.133 61.789 76.023 61.772 75.93 61.772 c
75.858 61.772 75.784 61.789 75.711 61.789 c
75.637 61.808 75.563 61.844 75.508 61.882 c
75.379 61.956 75.27 62.066 75.196 62.195 c
75.158 62.25 75.122 62.323 75.103 62.378 c
75.086 62.452 75.067 62.526 75.067 62.6 c
75.086 62.6 l
h
77.217 62.581 m
77.346 62.875 l
77.365 62.949 77.403 63.041 77.403 63.133 c
77.403 63.244 77.439 63.335 77.458 63.373 c
77.494 63.409 77.531 63.409 v
77.567 63.428 77.622 63.447 77.66 63.447 c
77.677 63.447 l
77.732 63.447 77.806 63.409 77.88 63.354 c
77.954 63.299 78.046 63.206 78.082 63.115 c
78.578 62.102 l
78.578 62.085 78.616 62.047 78.633 62.047 c
78.671 62.03 l
78.707 62.011 l
78.745 61.992 78.762 61.973 v
78.762 61.956 78.762 61.937 v
78.762 61.901 l
78.762 61.844 78.707 61.789 78.616 61.789 c
78.504 61.789 78.376 61.772 78.247 61.772 c
78.175 61.772 l
78.063 61.772 77.954 61.789 77.899 61.789 c
77.844 61.789 77.806 61.844 77.806 61.901 c
77.806 61.918 77.825 61.956 y
77.844 61.992 77.88 61.992 v
77.899 61.992 77.935 62.03 y
77.935 62.085 l
77.935 62.121 77.899 62.158 77.861 62.158 c
77.806 62.158 77.696 62.176 77.586 62.176 c
77.494 62.176 77.42 62.158 77.384 62.158 c
77.346 62.158 77.31 62.121 77.31 62.085 c
77.31 62.066 l
77.329 62.03 l
77.365 61.992 77.384 61.992 v
77.403 61.992 77.42 61.973 y
77.458 61.956 l
77.475 61.918 l
77.475 61.827 77.346 61.772 77.089 61.772 c
76.888 61.772 76.776 61.827 76.776 61.901 c
76.776 61.918 76.795 61.956 y
76.814 61.992 76.85 61.992 v
76.869 61.992 76.905 62.03 76.924 62.03 c
76.943 62.03 76.979 62.085 76.998 62.121 c
77.217 62.581 l
h
77.751 62.452 m
77.789 62.452 77.825 62.471 y
77.825 62.488 77.806 62.545 77.77 62.6 c
77.732 62.655 77.696 62.71 77.677 62.729 c
77.66 62.765 77.622 62.784 77.604 62.784 c
77.567 62.765 77.567 62.746 v
77.549 62.71 77.513 62.655 77.494 62.581 c
77.494 62.562 l
77.475 62.526 l
77.475 62.471 l
77.513 62.452 77.549 62.452 v
77.751 62.452 l
f*
62.539 65.727 m
63.479 65.999 l
62.628 66.42 l
62.642 66.586 l
63.879 65.963 l
62.945 65.691 l
63.82 65.264 l
62.492 64.863 l
62.506 65.031 l
63.417 65.299 l
62.539 65.727 l
h
63.823 67.972 m
63.019 67.901 l
63.095 68.062 l
63.702 68.114 l
63.352 68.615 l
63.426 68.774 l
63.889 68.112 l
64.377 67.884 l
64.312 67.745 l
63.823 67.972 l
h
64.12 69.924 m
64.282 70.124 l
64.336 70.191 64.395 70.249 64.46 70.298 c
64.529 70.348 64.602 70.384 64.677 70.404 c
64.757 70.426 64.841 70.43 64.928 70.414 c
64.972 70.406 65.015 70.391 65.058 70.37 c
65.102 70.349 65.145 70.321 65.188 70.286 c
65.2 70.277 l
65.281 70.211 65.344 70.131 65.388 70.038 c
65.432 69.942 65.446 69.835 65.428 69.716 c
65.41 69.598 65.351 69.478 65.253 69.356 c
65.081 69.144 l
64.12 69.924 l
h
64.327 69.955 m
65.069 69.353 l
65.128 69.426 l
65.239 69.564 65.291 69.698 65.282 69.828 c
65.273 69.955 65.215 70.062 65.107 70.15 c
65.1 70.156 l
65.041 70.203 64.982 70.235 64.921 70.252 c
64.86 70.27 64.798 70.272 64.733 70.26 c
64.607 70.235 64.488 70.154 64.375 70.015 c
64.327 69.955 l
h
66.186 71.977 m
67.373 71.195 l
67.232 71.106 l
66.947 71.294 l
66.467 70.994 l
66.512 70.656 l
66.369 70.567 l
66.186 71.977 l
h
66.366 71.689 m
66.447 71.148 l
66.819 71.381 l
66.366 71.689 l
h
68.692 73.084 m
69.269 72.293 l
69.373 73.238 l
69.535 73.281 l
69.373 71.905 l
68.798 72.69 l
68.695 71.72 l
67.865 72.833 l
68.028 72.876 l
68.591 72.111 l
68.692 73.084 l
h
70.984 73.391 m
71.842 72.349 l
71.906 73.265 l
72.064 73.254 l
71.974 71.968 l
71.11 73.007 l
71.046 72.084 l
70.893 72.095 l
70.984 73.391 l
h
73.483 72.867 m
73.63 72.819 l
73.248 71.642 l
73.101 71.689 l
73.483 72.867 l
h
75.201 70.865 m
75.104 70.71 l
74.987 70.715 74.88 70.747 74.784 70.807 c
74.685 70.869 74.608 70.952 74.554 71.056 c
74.5 71.16 74.475 71.272 74.48 71.393 c
74.483 71.5 74.512 71.597 74.567 71.684 c
74.576 71.699 74.582 71.709 74.585 71.713 c
74.622 71.773 74.667 71.824 74.72 71.865 c
74.768 71.903 74.823 71.933 74.883 71.956 c
74.997 71.997 75.105 72.009 75.208 71.993 c
75.311 71.977 75.398 71.946 75.471 71.901 c
75.571 71.838 75.648 71.758 75.699 71.663 c
75.604 71.51 l
75.566 71.63 75.494 71.723 75.389 71.789 c
75.352 71.813 75.313 71.83 75.273 71.841 c
75.234 71.853 75.192 71.859 75.148 71.859 c
75.062 71.859 74.979 71.839 74.899 71.796 c
74.819 71.754 74.758 71.699 74.716 71.631 c
74.663 71.547 74.635 71.459 74.631 71.369 c
74.626 71.281 74.644 71.197 74.684 71.119 c
74.704 71.079 74.728 71.044 74.756 71.013 c
74.783 70.982 74.816 70.955 74.853 70.931 c
74.865 70.924 l
74.957 70.867 75.069 70.847 75.201 70.865 c
h
76.837 70.444 m
76.643 70.667 l
76.75 70.76 l
77.238 70.198 l
77.131 70.105 l
76.937 70.329 l
76.11 69.609 l
76.01 69.724 l
76.837 70.444 l
h
78.373 68.389 m
77.695 67.683 l
78.642 67.744 l
78.713 67.592 l
77.331 67.513 l
78.004 68.217 l
77.032 68.149 l
77.982 69.161 l
78.053 69.008 l
77.398 68.32 l
78.373 68.389 l
h
78.909 65.559 m
78.903 65.628 78.885 65.69 78.856 65.745 c
78.826 65.8 78.786 65.849 78.735 65.892 c
78.683 65.934 78.626 65.966 78.562 65.985 c
78.497 66.005 78.43 66.013 78.364 66.007 c
78.276 65.999 78.195 65.97 78.121 65.919 c
78.047 65.868 77.992 65.802 77.954 65.723 c
77.916 65.644 77.901 65.56 77.909 65.471 c
77.917 65.383 77.946 65.302 77.997 65.23 c
78.048 65.158 78.114 65.103 78.194 65.066 c
78.275 65.029 78.36 65.014 78.45 65.022 c
78.52 65.028 78.585 65.047 78.645 65.078 c
78.701 65.106 78.751 65.146 78.794 65.198 c
78.836 65.246 78.867 65.301 78.887 65.364 c
78.908 65.427 78.915 65.492 78.909 65.559 c
h
79.05 65.571 m
79.057 65.484 79.048 65.399 79.021 65.317 c
78.995 65.236 78.955 65.163 78.903 65.099 c
78.851 65.036 78.787 64.983 78.71 64.942 c
78.634 64.901 78.552 64.876 78.464 64.868 c
78.375 64.861 78.292 64.87 78.213 64.896 c
78.134 64.922 78.06 64.964 77.992 65.02 c
77.928 65.074 77.876 65.138 77.836 65.213 c
77.796 65.288 77.772 65.37 77.764 65.459 c
77.754 65.576 77.774 65.687 77.823 65.79 c
77.872 65.893 77.943 65.978 78.037 66.043 c
78.132 66.111 78.236 66.15 78.351 66.16 c
78.465 66.17 78.575 66.15 78.68 66.101 c
78.785 66.051 78.87 65.981 78.936 65.889 c
79.001 65.797 79.039 65.691 79.05 65.571 c
f*
64.887 59.523 m
65.893 59.879 l
65.121 58.812 l
65.011 58.93 l
65.516 59.598 l
64.637 59.29 l
65.009 60.147 l
64.302 59.691 l
64.196 59.805 l
65.314 60.502 l
64.887 59.523 l
h
66.661 59.202 m
67.218 58.84 l
67.141 58.721 l
66.713 59 l
66.524 58.709 l
66.942 58.438 l
66.865 58.32 l
66.448 58.591 l
66.193 58.198 l
66.621 57.92 l
66.544 57.801 l
65.987 58.163 l
66.661 59.202 l
h
67.947 58.461 m
68.191 58.377 l
68.272 58.349 68.346 58.313 68.414 58.27 c
68.485 58.222 68.543 58.166 68.589 58.102 c
68.637 58.034 68.669 57.956 68.684 57.869 c
68.691 57.825 68.692 57.779 68.687 57.731 c
68.682 57.683 68.671 57.633 68.653 57.581 c
68.648 57.566 l
68.614 57.467 68.56 57.381 68.488 57.308 c
68.413 57.233 68.317 57.184 68.2 57.16 c
68.082 57.137 67.95 57.15 67.802 57.201 c
67.544 57.29 l
67.947 58.461 l
h
68.047 58.277 m
67.736 57.373 l
67.825 57.343 l
67.992 57.285 68.136 57.283 68.255 57.336 c
68.371 57.387 68.451 57.479 68.497 57.61 c
68.5 57.619 l
68.524 57.69 68.534 57.757 68.53 57.82 c
68.525 57.883 68.506 57.943 68.472 57.999 c
68.406 58.11 68.289 58.194 68.12 58.252 c
68.047 58.277 l
h
69.883 57.261 m
69.579 58.01 l
69.756 57.985 l
69.983 57.419 l
70.359 57.9 l
70.533 57.876 l
70.035 57.24 l
69.96 56.706 l
69.808 56.727 l
69.883 57.261 l
h
72.263 57.05 m
72.289 56.87 l
72.196 56.798 72.093 56.754 71.981 56.738 c
71.865 56.722 71.753 56.736 71.645 56.78 c
71.537 56.825 71.446 56.895 71.371 56.991 c
71.306 57.075 71.266 57.168 71.252 57.27 c
71.249 57.287 71.247 57.299 71.247 57.304 c
71.237 57.374 71.239 57.441 71.252 57.507 c
71.265 57.567 71.287 57.625 71.319 57.682 c
71.38 57.786 71.455 57.866 71.544 57.919 c
71.634 57.973 71.72 58.005 71.805 58.017 c
71.922 58.034 72.032 58.022 72.132 57.982 c
72.157 57.804 l
72.051 57.871 71.937 57.897 71.813 57.879 c
71.77 57.873 71.729 57.862 71.691 57.845 c
71.654 57.828 71.618 57.806 71.584 57.777 c
71.518 57.723 71.468 57.653 71.434 57.569 c
71.4 57.486 71.388 57.404 71.399 57.325 c
71.413 57.226 71.448 57.141 71.503 57.069 c
71.556 56.999 71.623 56.947 71.704 56.912 c
71.745 56.895 71.786 56.883 71.827 56.877 c
71.868 56.871 71.91 56.871 71.954 56.878 c
71.968 56.879 l
72.075 56.895 72.174 56.951 72.263 57.05 c
h
73.473 58.303 m
72.974 58.101 l
72.921 58.232 l
73.654 58.529 l
73.483 57.276 l
74.065 57.512 l
74.118 57.381 l
73.304 57.052 l
73.473 58.303 l
h
74.318 58.897 m
75.644 58.651 l
75.105 59.394 l
75.233 59.487 l
75.99 58.443 l
74.662 58.684 l
75.205 57.935 l
75.081 57.845 l
74.318 58.897 l
h
75.87 60.068 m
76.297 60.577 l
76.406 60.486 l
76.078 60.095 l
76.343 59.872 l
76.662 60.254 l
76.77 60.163 l
76.451 59.782 l
76.809 59.481 l
77.137 59.872 l
77.245 59.781 l
76.818 59.272 l
75.87 60.068 l
f*
EMC
0 G
0 J 0 j 0.216 w 10 M []0 d
/GS2 gs
62.352 112.571 m
518.76 112.571 l
S
BT
7.5 0 0 7.5 62.352 101.303 Tm
-0.0003 Tc
-0.003 Tw
(Adres do korespondencji \(Address for correspondence\): dr med. Zbigniew ylicz, prof. AM)Tj
0 -1.3248 TD
-0.0005 Tc
0 Tw
(Katedra i Zakad Opieki Paliatywnej AM w Bydgoszczy)Tj
0 -1.3344 TD
-0.0009 Tc
(e-mail: z.zylicz@chello.nl)Tj
3.7824 -1.9008 TD
0.0001 Tc
-0.0022 Tw
(Polska Medycyna Paliatywna 2004, 3, 2, 165170)Tj
0 -1.3344 TD
-0.0002 Tc
-0.0011 Tw
(Copyright 2004 Via Medica, ISSN 1644115X)Tj
10 0 0 10 62.352 734.4711 Tm
-0.0011 Tc
-0.01 Tw
(Zbigniew ylicz)Tj
7.5 0 0 7.5 62.352 721.4391 Tm
-0.0003 Tc
-0.0024 Tw
(Katedra i Zakad Opieki Paliatywnej Akademii Medycznej im. Ludwika Rydygiera w Bydgoszczy)Tj
ET
62.352 706.859 m
518.76 706.859 l
S
BT
7.5 0 0 7.5 62.352 712.4391 Tm
-0.0001 Tc
-0.0053 Tw
(\(Chair and Department of Palliative Care, The Ludwik Rydygier University of Medical Sciences, Bydgoszcz, Poland\))Tj
/F1 1 Tf
24 0 0 24 62.352 658.4391 Tm
-0.0025 Tc
0.0396 Tw
(Antagonici opioidowi)Tj
0 -1.251 TD
-0.0017 Tc
0.0115 Tw
(jako leki przeczyszczajce.)Tj
T*
-0.0024 Tc
0.0188 Tw
(Analiza dostpnych danych)Tj
12 0 0 12 62.352 567.071 Tm
-0.0008 Tc
-0.0005 Tw
(Opioid antagonists as laxatives. An analysis of the available data)Tj
/F3 1 Tf
9.5 0 0 9.5 62.352 496.943 Tm
0.0001 Tc
0 Tw
(Streszczenie)Tj
/F2 1 Tf
8 0 0 8 90.72 485.423 Tm
-0.0004 Tc
0.174 Tw
(Analgetyki opioidowe s podstawowymi lekami w terapii blu u osb z zaawansowanymi chorobami,)Tj
0 -1.377 TD
0.1931 Tw
(wtym nowotworowymi. Leki te wywouj take objawy uboczne. Do najbardziej dokuczliwych nale)Tj
T*
-0.0005 Tc
-0.0031 Tw
(zaparcia. Przyczyna zapar zwizana jest cile z interakcj lekw opioidowych z receptorami opioidowymi)Tj
0 -1.368 TD
0.1269 Tw
(na zakoczeniach wkien czuciowych. Antagonici receptorw opioidowych dziaajcy na obwodzie s)Tj
0 -1.377 TD
-0.0004 Tc
0.2169 Tw
(wtej sytuacji potencjalnymi lekami przeczyszczajcymi. Nalokson \(NLX\) podany doustnie u niektrych)Tj
T*
-0.0005 Tc
-0.0447 Tw
[(pacjentw powoduje zmniejszenie zapar, ale cz tych chorych odczuwa objawy odstawienia, a niektrzy)]TJ
T*
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(\()Tj
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7.5 0 0 7.5 243.288 31.247 Tm
0 g
/GS2 gs
-0.0001 Tc
0 Tw
(www.pmp.viamedica.pl)Tj
8.5 0 0 8.5 535.32 31.247 Tm
-0.0041 Tc
(167)Tj
7.5 0 0 7.5 141.264 771.0471 Tm
0.0005 Tc
0.0034 Tw
(Zbigniew ylicz )Tj
/F5 1 Tf
8.6592 0 TD
-0.0013 Tc
0.0048 Tw
(Antagonici opioidowi jako leki przeczyszczajce. Analiza dostpnych danych)Tj
/F2 1 Tf
9 0 0 9 316.008 734.255 Tm
-0.0003 Tc
0.0453 Tw
(Different opioids may interact in different ways)Tj
-1.568 -1.4 TD
0.0003 Tc
0.0703 Tw
(with the peripheral opioid receptors. Fentanyl, be-)Tj
T*
-0.0004 Tc
0.0786 Tw
(ing very lipophilic, is probably more rapidly absor-)Tj
T*
0.0003 Tc
0.1611 Tw
(bed through the blood-brain barrier and has less)Tj
T*
0 Tc
-0.0064 Tw
(effect on the peripheral receptors. This may explain)Tj
T*
0.0002 Tc
0.1911 Tw
(why, during observations, fentanyl produced less)Tj
T*
-0.0072 Tc
-0.0746 Tw
(constipatory effect than morphine [14]. On the other)Tj
T*
0.0003 Tc
-0.0166 Tw
(hand, no comparative studies have yet been under-)Tj
T*
-0.0003 Tc
0.0055 Tw
(taken at equianalgesic doses.)Tj
/F3 1 Tf
11 0 0 11 301.896 604.079 Tm
-0.0002 Tc
0.0181 Tw
(Opioid antagonists)Tj
/F2 1 Tf
9 0 0 9 316.008 583.055 Tm
0.0006 Tc
-0.0602 Tw
(No pure endogenous opioid antagonists have so)Tj
-1.568 -1.4 TD
-0.0001 Tc
0.0881 Tw
(far been identified. The affinity of opioid peptides)Tj
T*
-0.0003 Tc
0.0417 Tw
[(may be stronger or weaker and they may compete)]TJ
T*
0.0005 Tc
0.0271 Tw
(at the same receptors. In this situation the conten-)Tj
T*
0 Tc
0.1404 Tw
(ders with a stronger affinity and weaker receptor)Tj
T*
-0.0001 Tc
-0.0296 Tw
(stimulation may act as competitive inhibitors. Nalo-)Tj
T*
0.0003 Tc
0.1236 Tw
(xone \(NLX\), a known opioid antagonist, is a drug)Tj
T*
0.0001 Tc
-0.0312 Tw
(with a very high affinity and low stimulation poten-)Tj
T*
-0.0001 Tc
0.0679 Tw
(tial. NLX antagonises the activity of most if not all)Tj
T*
0.0008 Tc
0.2092 Tw
(known endogenous and exogenous opioids. It is)Tj
T*
-0.0044 Tc
-0.075 Tw
(used to reverse opioid effects, mainly toxicity in drug)Tj
T*
-0.0001 Tc
-0.0314 Tw
(addicts. As a rule this drug elicits a strong abstinen-)Tj
T*
-0.0002 Tc
-0.0166 Tw
(ce syndrome. NLX is an injectable drug with a rapid)Tj
T*
0.0004 Tc
0.0179 Tw
(onset and a short half-life. If used to neutralise the)Tj
T*
0.0024 Tc
0.225 Tw
(toxicity of slow-release opioids, such as fentanyl)Tj
T*
0.0003 Tc
0.1841 Tw
(patch or morphine sulphate tablets, it should be)Tj
T*
0.0969 Tw
(used in a continuous infusion. Naloxone is rapidly)Tj
T*
-0.0001 Tc
0.1593 Tw
(inactivated by glucuronidation [15] and the main)Tj
T*
0 Tc
0.0244 Tw
(metabolite, NLX-3-glucuronide, is inactive [16, 17].)Tj
T*
-0.0002 Tc
0.141 Tw
(This process may take place in the liver, reducing)Tj
T*
-0.0001 Tc
-0.0037 Tw
(naloxone bio-availability to less than 3% [15].)Tj
1.568 -1.4 TD
-0.0004 Tc
0.0463 Tw
(Injected parenterally, the drug may bypass liver)Tj
-1.568 -1.4 TD
0 Tc
0.001 Tw
(glucuronidation and may pass the blood-brain bar-)Tj
T*
0.0002 Tc
0.1166 Tw
(rier. The brain tissue is able to glucuronidate NLX)Tj
T*
-0.0001 Tc
-0.0722 Tw
(and inactivate it [18]. So orally administered naloxo-)Tj
T*
-0.0003 Tc
0.0056 Tw
(ne would be able to act only topically, immediately)Tj
T*
0.0001 Tc
0.0549 Tw
(before its inactivation in the liver. NLX is absorbed)Tj
T*
0.0004 Tc
-0.042 Tw
(in the jejunum and the opioid receptors responsible)Tj
T*
-0.0587 Tw
(for constipation are in the colon. It is thus probable,)Tj
T*
0.0002 Tc
0.1563 Tw
(that NLX glucuronides are excreted with bile and)Tj
T*
0.0001 Tc
-0.0186 Tw
(that colonic bacteria deglucuronidate them to NLX.)Tj
T*
0.0004 Tc
-0.0102 Tw
[(However, this hypothesis is as yet unproven.)]TJ
/F3 1 Tf
9.5 0 0 9.5 301.896 167.255 Tm
-0.0006 Tc
0.0171 Tw
(Clinical trials with opioid antagonists)Tj
/F2 1 Tf
9 0 0 9 316.008 154.655 Tm
-0.0132 Tc
0.1741 Tw
(Orally administered NLX was found effective in)Tj
-1.568 -1.4 TD
-0.0127 Tc
0.1822 Tw
(the amelioration of opioid-induced constipation in)Tj
T*
-0.0133 Tc
-0.075 Tw
(several case studies and in open label studies [1922].)Tj
1.568 -1.4 TD
0.0002 Tc
-0.0673 Tw
(In the study by Sykes [23] the naloxone dose was)Tj
-1.568 -1.4 TD
0.0001 Tc
0.0198 Tw
(calculated as the percentage of the morphine dose)Tj
T*
0.0004 Tc
0.0095 Tw
(used. 17 patients entered this double blind, rando-)Tj
T*
0.0002 Tc
-0.0117 Tw
[(mised trial. Naloxone at doses of 10% or less of the)]TJ
T*
-0.0001 Tc
-0.0683 Tw
(prevailing morphine dose was ineffective as a laxati-)Tj
-26.616 74.2 TD
-0.0003 Tc
0.1986 Tw
(przypadku oddziaywanie antagonistyczne na ob-)Tj
0 -1.4 TD
0.0001 Tc
-0.0534 Tw
(wodowe receptory opioidowe moe nie wystarczy.)Tj
1.568 -1.4 TD
-0.0102 Tc
(Obwodowe receptory opioidowe mog by take)Tj
-1.568 -1.4 TD
-0.0098 Tc
-0.0678 Tw
(odpowiedzialne za analgezj obwodow [13]. Stoso-)Tj
T*
-0.0101 Tc
0.1867 Tw
(wanie maych dawek opioidw podawanych miej-)Tj
T*
0.2046 Tw
(scowo, bezporednio na bolce miejsce moe by)Tj
T*
-0.0102 Tc
-0.0194 Tw
(przydatn metod zwalczania blu, ktra nie wywo-)Tj
T*
-0.01 Tc
-0.0611 Tw
(uje centralnych i systemowych objaww ubocznych,)Tj
T*
-0.011 Tc
0.0222 Tw
(takich jak zaparcia.)Tj
1.568 -1.4 TD
-0.0003 Tc
0.0992 Tw
(Rne opioidy mog mie rny wpyw na ob-)Tj
-1.568 -1.4 TD
0.0003 Tc
0.0223 Tw
(wodowe receptory opioidowe. Fentanyl jest prepa-)Tj
T*
-0.0004 Tc
0.1037 Tw
(ratem bardzo lipofilnym, ktry bez trudu przenika)Tj
T*
0.2249 Tw
(przez barier krew-mzg. Wydaje si, e wanie)Tj
T*
-0.0002 Tc
0.1148 Tw
(dlatego, i dziaa sabiej na receptory obwodowe,)Tj
T*
-0.0001 Tc
-0.0195 Tw
[(powoduje mniej zapar ni morfina [14]. Z kolei nie)]TJ
T*
0.0003 Tc
0.1139 Tw
(przeprowadzono bada, w ktrych porwnywano)Tj
T*
0 Tc
0.1844 Tw
(by wystpowanie zapar przy podawaniu rwno-)Tj
T*
-0.0007 Tc
0.0056 Tw
(wanych dawek analgetycznych.)Tj
/F3 1 Tf
11 0 0 11 62.352 490.679 Tm
-0.0004 Tc
0.0182 Tw
(Antagonici opioidowi)Tj
/F2 1 Tf
9 0 0 9 76.464 469.655 Tm
0.0004 Tc
-0.0145 Tw
(Nie poznano dotd peptydu endogennego, kt-)Tj
-1.568 -1.4 TD
-0.0005 Tc
0.0589 Tw
(ry dziaaby jak czysty antagonista. Powinowactwo)Tj
T*
0.0001 Tc
0.1944 Tw
(peptydw opioidowych do receptorw moe by)Tj
T*
-0.0002 Tc
0.027 Tw
(silne lub sabe, a rne peptydy mog konkurowa)Tj
T*
-0.0003 Tc
0.1461 Tw
(o przyczenie do tych samych receptorw. W tej)Tj
T*
-0.0002 Tc
0.1039 Tw
[(sytuacji peptydy o silnym powinowactwie, a za to)]TJ
T*
-0.0006 Tc
0.0911 Tw
(sabiej stymulujce receptor, dziaaj jak kompety-)Tj
T*
0.0001 Tc
0.1009 Tw
[(tywni antagonici. Nalokson \(NLX\) jest znanym le-)]TJ
T*
-0.0006 Tc
0.0989 Tw
(kiem syntetycznym cechujcym si wysokim powi-)Tj
T*
0.0004 Tc
0.2022 Tw
(nowactwem do receptorw opioidowych, ale nie)Tj
T*
-0.0016 Tc
-0.075 Tw
(stymulujcym ich. Dlatego NLX znosi dziaanie wik-)Tj
T*
-0.0001 Tc
0.0555 Tw
(szoci, jeeli nie wszystkich, znanych endogennych)Tj
T*
0.0001 Tc
0.0952 Tw
(i egzogennych opioidw. Lek ten uywany jest do)Tj
T*
-0.0054 Tc
-0.0744 Tw
(odwracania dziaania opioidw, gwnie w przypad-)Tj
T*
-0.0003 Tc
0.0593 Tw
(ku wystpienia dziaa toksycznych u osb uzale-)Tj
T*
0 Tc
0.1593 Tw
(nionych od narkotykw. Nalokson w zasadzie za-)Tj
T*
0.0004 Tc
0.0722 Tw
(wsze powoduje u tych pacjentw powstanie obja-)Tj
T*
0.0001 Tc
0.0138 Tw
(ww odstawienia. Lek ten mona podawa jedynie)Tj
T*
-0.0004 Tc
0.0988 Tw
[(pozajelitowo. Dziaa szybko, ale charakteryzuje si)]TJ
T*
-0.0006 Tc
-0.0555 Tw
[(take bardzo krtkim czasem ptrwania. Jeeli uy-)]TJ
T*
-0.0004 Tc
-0.063 Tw
(wany jest do neutralizacji dziaania tabletek morfiny)Tj
T*
-0.0002 Tc
0.1564 Tw
(o przeduonym dziaaniu, to naley go podawa)Tj
T*
0.0371 Tw
[(w pompie infuzyjnej przez duszy okres. Nalokson)]TJ
T*
0.1 Tw
(jest szybko metabolizowany do nieaktywnych glu-)Tj
T*
0 Tc
-0.0584 Tw
(kuronianw [15], a gwnym metabolitem jest NLX-)Tj
T*
0.0002 Tc
0.0071 Tw
(-3-glukuronian [16, 17]. Proces ten zachodzi w w-)Tj
T*
0.0005 Tc
0.0528 Tw
(trobie i powoduje obnienie si dostpnoci biolo-)Tj
T*
-0.0002 Tc
-0.0022 Tw
(gicznej leku do poniej 3% [15].)Tj
1.568 -1.4 TD
-0.0021 Tc
-0.0744 Tw
(Nalokson podany pozajelitowo omija proces glu-)Tj
-1.568 -1.4 TD
-0.0001 Tc
0.0423 Tw
(kuronizacji w wtrobie i jest w stanie przej przez)Tj
T*
-0.0004 Tc
0.0078 Tw
(barier krew-mzg. Tkanka mzgowa moe inakty-)Tj
T*
0.0002 Tc
-0.0611 Tw
(wowa NLX do glukuronianw [18]. Zatem NLX sto-)Tj
T*
0.0095 Tc
0.2255 Tw
(sowany doustnie moe dziaa tylko miejscowo,)Tj
ET
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BT
/F1 1 Tf
7.5 0 0 7.5 62.34 771.0471 Tm
0 g
/GS2 gs
-0.0006 Tc
0.0067 Tw
(Polska Medycyna Paliatywna 2004, tom 3, nr 2)Tj
24.1248 -98.64 TD
-0.0001 Tc
0 Tw
(www.pmp.viamedica.pl)Tj
8.5 0 0 8.5 28.356 31.247 Tm
-0.0041 Tc
(168)Tj
/F2 1 Tf
9 0 0 9 301.884 734.255 Tm
0 Tc
-0.0233 Tw
(ve. Oral naloxone at a daily dose of 20% of morphi-)Tj
0 -1.4 TD
0.0003 Tc
-0.0333 Tw
(ne was found to be laxative, but produced withdra-)Tj
T*
0.0001 Tc
-0.0032 Tw
(wal symptoms in 9 out of 12 patients.)Tj
1.576 -1.4 TD
-0.015 Tc
0.1372 Tw
(In a study by Meissner et al. [22] the NLX dose)Tj
-1.576 -1.4 TD
-0.0148 Tw
(administered to 17 constipated chronic pain patients)Tj
T*
0.0561 Tw
(using oral opioids was titrated from 9 up to 36 mg/)Tj
T*
0.2077 Tw
[(/)-11.9(day. In the 6-day observation period, on a stable)]TJ
T*
-0.0147 Tc
0.1215 Tw
(dose, the mean number of days with bowel move-)Tj
T*
0.0687 Tw
[(ment increased from 2.1 in the control period \(con)-6.8(-)]TJ
T*
-0.0145 Tc
0.0756 Tw
(ventional laxatives\) to 3.5 on naloxone \(p < 0.001\).)Tj
T*
-0.0148 Tc
0.0771 Tw
[(The need to use laxatives decreased. The mean )-6.8(N)-13.3(L)-13.3(X)]TJ
T*
0.0116 Tw
[(dose in these patients was 17.5 mg a day. The mean)]TJ
T*
0.188 Tw
(pain intensity did not change. However, moderate)Tj
T*
-0.015 Tc
-0.0056 Tw
(withdrawal symptoms were observed in 4 patients.)Tj
1.576 -1.4 TD
-0.0051 Tc
0.1834 Tw
(In another study, that performed by Liu et al.)Tj
-1.576 -1.4 TD
-0.0049 Tc
0.0508 Tw
([24], only 9 constipated patients were treated with)Tj
T*
0.1673 Tw
(low doses of NLX \(612 mg/day\). All the patients)Tj
T*
-0.0042 Tc
0.1465 Tw
(who received oral NLX saw some improvement in)Tj
T*
-0.005 Tc
-0.075 Tw
(bowel movements. However, 3 out of 9 patients also)Tj
T*
-0.0072 Tc
-0.0746 Tw
(experienced a reversal of analgesia. One patient even)Tj
T*
-0.0112 Tc
-0.0744 Tw
(experienced complete analgesia reversal. The authors)Tj
T*
-0.0058 Tc
-0.0746 Tw
(also observed that patients who are on high doses of)Tj
T*
-0.0048 Tc
0.0334 Tw
(opioids are more vulnerable to the reversal of anal-)Tj
T*
-0.0044 Tc
-0.0075 Tw
(gesia even with low doses of naloxone.)Tj
1.576 -1.4 TD
-0.0002 Tc
0.0925 Tw
(A large controlled study, performed by Roxane)Tj
-1.576 -1.4 TD
0.0005 Tc
-0.0465 Tw
(in several European countries with oral NLX in opio-)Tj
T*
0.0001 Tc
0.1167 Tw
(id-constipated patients, was inconclusive and was)Tj
T*
0.0002 Tc
-0.0047 Tw
(discontinued. The reason for this is still unclear.)Tj
1.576 -1.4 TD
-0.0179 Tc
-0.0596 Tw
[(Naltrexone \(NTX\) is an orally acting opioid antago-)]TJ
-1.576 -1.4 TD
0.0055 Tw
(nist and is indicated for the treatment of alcohol and)Tj
T*
0.0354 Tw
(opioid dependence. In a manner similar to NLX, NTX)Tj
T*
-0.0181 Tc
-0.037 Tw
[(will precipitate acute withdrawal reactions in patients)]TJ
T*
-0.0175 Tc
-0.0062 Tw
(dependent on opioids and also in patients with chro-)Tj
T*
-0.0084 Tw
(nic pruritus [25]. The doses needed to reverse opioid-)Tj
T*
-0.0182 Tc
-0.0122 Tw
[(-)-24.2(induced adverse effects, including constipation, may)]TJ
T*
-0.0176 Tc
-0.0035 Tw
(be lower than the doses needed to reverse analgesia.)Tj
T*
0.0521 Tw
(No studies with NTX have yet been undertaken. This)Tj
T*
-0.0179 Tc
0.0507 Tw
[(antagonist does not seem to be suitable as an orally)]TJ
T*
-0.0034 Tw
(active opioid antagonist with laxative properties.)Tj
1.576 -1.4 TD
0.0152 Tc
0.824 Tw
(However, its derivative, methylnaltrexone)Tj
-1.576 -1.4 TD
0.0004 Tc
0.0373 Tw
(\(MTNTX\) is an opioid antagonist with orphan drug)Tj
T*
0.0002 Tc
0.018 Tw
(status. It is currently being investigated for the tre-)Tj
T*
-0.0001 Tc
0.0732 Tw
(atment of opioid-induced adverse effects [26, 27].)Tj
T*
0.0003 Tc
0.0041 Tw
(The addition of the methyl group to NTX decreases)Tj
T*
0.0002 Tc
-0.0001 Tw
(its lipophilicity and prevents its uptake through the)Tj
T*
-0.058 Tw
(blood-brain barrier. The effects of MTNTX are there-)Tj
T*
-0.0278 Tw
(fore limited to the reversal of the peripheral opioid-)Tj
T*
0.013 Tw
(-induced adverse effects. The obvious potential ad-)Tj
T*
0.0001 Tc
-0.0086 Tw
(vantage of MTNTX is its lack of interaction with the)Tj
T*
-0.0073 Tc
-0.074 Tw
[(central opioid analgesia. )-7.2(Several studies have already)]TJ
T*
0.0003 Tc
-0.0342 Tw
(been performed with MTNTX, and some other trials)Tj
T*
-0.0002 Tc
-0.0019 Tw
(are still ongoing [28].)Tj
1.576 -1.4 TD
0.0004 Tc
0.112 Tw
(Interestingly, MTNTX was found to reverse the)Tj
-1.576 -1.4 TD
-0.0001 Tc
0.0467 Tw
(opioid-induced inhibition of gastric emptying [29].)Tj
-26.616 74.2 TD
0.0977 Tw
[(przed inaktywacj w wtrobie. Nalokson wchania)]TJ
0 -1.4 TD
-0.0004 Tc
0.1334 Tw
(si w jelicie cienkim, podczas gdy receptory opio-)Tj
T*
-0.0008 Tc
-0.075 Tw
(idowe odpowiedzialne za zaparcie znajduj si wje-)Tj
T*
-0.0002 Tc
0.0388 Tw
(licie grubym. Dlatego te moliwe jest, e glukuro-)Tj
T*
-0.0003 Tc
0.0625 Tw
(niany NLX s wydalane wraz z ci i poddawane)Tj
T*
0.0004 Tc
0.2255 Tw
(deglukuronizacji przez bakterie w jelicie grubym.)Tj
T*
0 Tc
-0.0045 Tw
(Jednak jeszcze nie sprawdzono tej hipotezy.)Tj
/F3 1 Tf
9.5 0 0 9.5 62.34 633.455 Tm
-0.0009 Tc
0.0185 Tw
(Prby kliniczne z antagonistami opioidowymi)Tj
/F2 1 Tf
9 0 0 9 76.524 620.855 Tm
-0.0063 Tc
-0.0745 Tw
(W kilku doniesieniach kazuistycznych i badaniach)Tj
-1.576 -1.4 TD
0.0003 Tc
-0.0723 Tw
[(niekontrolowanych wykazano, e nalokson zastoso-)]TJ
T*
0.0001 Tc
0.2255 Tw
[(wany doustnie moe zmniejszy objawy zaparcia)]TJ
T*
0.0004 Tc
-0.0185 Tw
(spowodowanego podaniem opioidw [1922].)Tj
1.576 -1.4 TD
-0.0004 Tc
0.2256 Tw
(W badaniu opublikowanym przez Sykesa [23])Tj
-1.576 -1.4 TD
-0.0002 Tc
-0.0699 Tw
(dawk NLX wyliczono jako stay procent dawki mor-)Tj
T*
-0.0003 Tc
0.0019 Tw
(finy uywanej do zwalczania blu. Tym randomizo-)Tj
T*
-0.0001 Tc
-0.0486 Tw
(wanym, kontrolowanym przez placebo, przeprowa-)Tj
T*
-0.0002 Tc
0.0972 Tw
(dzonym za pomoc podwjnie lepej prby bada-)Tj
T*
0.0002 Tc
0.1815 Tw
(niem objto 17 pacjentw. Nalokson w dawkach)Tj
T*
-0.0002 Tc
-0.0048 Tw
(rwnych lub mniejszych ni 10% dawki morfiny nie)Tj
T*
-0.0005 Tc
0.0569 Tw
(dziaa przeczyszczajco, natomiast doustna dzien-)Tj
T*
-0.0004 Tc
0.0132 Tw
(na dawka NLX rwna 20% dawki morfiny miaa ta-)Tj
T*
0.0001 Tc
0.05 Tw
(kie dziaanie, ale u 9 spord 12 chorych powodo-)Tj
T*
0 Tc
-0.0055 Tw
(waa jednoczenie objawy odstawienia.)Tj
1.576 -1.4 TD
-0.0132 Tc
-0.0277 Tw
(W badaniu Meissnera i wsp. [22] 17 osobom cier-)Tj
-1.576 -1.4 TD
-0.0134 Tc
0.0492 Tw
(picym z powodu zaparcia podano NLX w dawkach)Tj
T*
0.1597 Tw
(miareczkowanych, wynoszcych 936 mg/dob. Po)Tj
T*
-0.0161 Tc
-0.075 Tw
(znalezieniu odpowiedniej dawki chorych obserwowa-)Tj
T*
-0.0132 Tc
0.1007 Tw
(no przez 6 dni. rednia liczba dni z wyprnieniem)Tj
T*
-0.0405 Tw
(wzrosa z 2,1 w okresie kontrolnym \(przed podaniem)Tj
T*
-0.0129 Tc
0.0378 Tw
(NLX\) do 3,5 w okresie leczenia NLX \(p < 0,001\). Za-)Tj
T*
-0.0135 Tc
0.1666 Tw
(potrzebowanie na rodki przeczyszczajce zmalao.)Tj
T*
0.0019 Tc
0.3463 Tw
( rednia dawka NLX u tych pacjentw wynosia)Tj
T*
-0.0128 Tc
0.1433 Tw
(17,5mg/dob. rednie natenie blu nie zmienio)Tj
T*
-0.0131 Tc
0.0084 Tw
(si pod wpywem NLX, chocia u 4 chorych zaobser-)Tj
T*
-0.0128 Tc
-0.0167 Tw
(wowano objawy odstawienia.)Tj
1.576 -1.4 TD
-0.0004 Tc
0.12 Tw
[(W innym badaniu przeprowadzonym przez Liu)]TJ
-1.576 -1.4 TD
-0.0002 Tc
0.0682 Tw
(iwsp. [24] tylko 9 osb z zaparciami spowodowa-)Tj
T*
0.0001 Tc
-0.0434 Tw
(nymi podawaniem opioidw poddano leczeniu ma-)Tj
T*
-0.0008 Tc
0.2129 Tw
(ymi dawkami NLX \(612 mg/dob\). Wszyscy pa-)Tj
T*
-0.0006 Tc
0.0565 Tw
(cjenci objci t terapi odczuli dziaanie przeczysz-)Tj
T*
-0.0004 Tc
0.0525 Tw
(czajce. Pomimo to u 3 z 9 chorych wystpi take)Tj
T*
0.0004 Tc
0.1977 Tw
(nawrt blu. Jeden pacjent poinformowa nawet)Tj
T*
-0.0117 Tc
-0.0744 Tw
(o cakowitym braku dziaania przeciwblowego mor-)Tj
T*
-0.0001 Tc
0.0629 Tw
(finy. Autorzy zaobserwowali, e chorzy leczeni du-)Tj
T*
-0.0006 Tc
0.1593 Tw
[(ymi dawkami opioidw byli bardziej wraliwi na)]TJ
T*
0.0001 Tc
-0.0087 Tw
(odwrcenie analgezji i nawrt blu, nawet przy za-)Tj
T*
-0.0001 Tc
-0.0018 Tw
(stosowaniu maych dawek NLX.)Tj
1.576 -1.4 TD
-0.0458 Tw
(Bardzo obszernie zakrojone badanie przeprowa-)Tj
-1.576 -1.4 TD
-0.0002 Tc
0.0294 Tw
(dzone w kilku krajach europejskich w latach 2000)Tj
T*
-0.0004 Tc
-0.0289 Tw
(2001 przez Roxane Laboratories, dotyczce dziaa-)Tj
T*
-0.0139 Tw
(nia przeczyszczajcego NLX nie zostao niestety do-)Tj
T*
0 Tc
-0.0311 Tw
(koczone i opublikowane. Przyczyna takiego post-)Tj
T*
0.0002 Tc
-0.0018 Tw
(powania nie jest jasna.)Tj
ET
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/F1 1 Tf
7.5 0 0 7.5 243.288 31.247 Tm
0 g
/GS2 gs
-0.0001 Tc
0 Tw
(www.pmp.viamedica.pl)Tj
8.5 0 0 8.5 535.32 31.247 Tm
-0.0041 Tc
(169)Tj
7.5 0 0 7.5 141.264 771.0471 Tm
0.0005 Tc
0.0034 Tw
(Zbigniew ylicz )Tj
/F5 1 Tf
8.6592 0 TD
-0.0013 Tc
0.0048 Tw
(Antagonici opioidowi jako leki przeczyszczajce. Analiza dostpnych danych)Tj
/F2 1 Tf
9 0 0 9 301.896 734.255 Tm
0.0003 Tc
-0.0143 Tw
(In this controlled study 11 patients were evaluated.)Tj
0 -1.4 TD
0.0002 Tc
-0.0271 Tw
(The study subjects were treated either with a place-)Tj
T*
-0.0088 Tc
-0.0747 Tw
(bo and morphine or morphine and MTNTX in a cross-)Tj
T*
-0.0003 Tc
0.0296 Tw
(over fashion. Significant delays in gastric emptying)Tj
T*
0.0005 Tc
0.0127 Tw
(were observed in the group treated with morphine)Tj
T*
-0.0003 Tc
0.0802 Tw
(and the placebo. This delay was nearly completely)Tj
T*
0.0003 Tc
0.1117 Tw
(reversed by the addition of MTNTX \(p < 0.04\). In)Tj
T*
-0.0003 Tc
0.0625 Tw
(addition, paracetamol absorption was significantly)Tj
T*
0.0001 Tc
-0.0343 Tw
[(delayed when patients received morphine and peak)]TJ
T*
0.0005 Tc
0.0222 Tw
(concentrations were less than those in the placebo)Tj
T*
-0.0019 Tw
(group \(p < 0.03\).)Tj
1.568 -1.4 TD
0.0001 Tc
-0.0033 Tw
(In a double blind, randomised, placebo-control-)Tj
-1.568 -1.4 TD
0 Tc
0.1723 Tw
[(led study by Yuan et al. [30] intravenous MTNTX)]TJ
T*
0.0002 Tc
0.1214 Tw
(was administered to 22 subjects on a methadone)Tj
T*
-0.0003 Tc
-0.0027 Tw
(maintenance programme. MTNTX improved gastric)Tj
T*
0 Tc
0.0921 Tw
(emptying, nausea and overall gut transit time. No)Tj
T*
0.0002 Tc
-0.001 Tw
(opioid withdrawal symptoms were observed in this)Tj
T*
-0.0018 Tc
0 Tw
(study.)Tj
1.568 -1.4 TD
-0.0002 Tc
-0.0056 Tw
(ADL 9-2698 is a novel peripherally acting opioid)Tj
-1.568 -1.4 TD
0.0003 Tc
-0.058 Tw
(antagonist. This drug is expected to be used in futu-)Tj
T*
0.0001 Tc
0.1516 Tw
(re for the alleviation of peripheral opioid adverse)Tj
T*
-0.0061 Tc
-0.075 Tw
(effects, including constipation. Clinical trials are now)Tj
T*
-0.0002 Tc
-0.0055 Tw
(ongoing [31, 32].)Tj
/F3 1 Tf
11 0 0 11 301.896 427.679 Tm
0.0009 Tc
0 Tw
(Conclusion)Tj
/F2 1 Tf
9 0 0 9 316.008 406.655 Tm
0.0099 Tc
-0.0478 Tw
(Opioid antagonists acting peripherally have the)Tj
-1.568 -1.4 TD
0.0102 Tc
0.0125 Tw
(potential to alleviate opioid-induced constipation.)Tj
T*
0.01 Tc
0.1707 Tw
(Oral NLX produces some laxation, but some pa-)Tj
T*
-0.0722 Tw
(tients suffer from withdrawal symptoms and rever-)Tj
T*
0.0097 Tc
-0.025 Tw
(sal of analgesia. NTX is a centrally and peripherally)Tj
T*
0.0101 Tc
-0.0072 Tw
(acting opioid antagonist and this is why it is of no)Tj
T*
0.0102 Tc
0.225 Tw
(use as laxative. However, its derivative, MTNTX,)Tj
T*
0.0097 Tc
0.0007 Tw
(acts peripherally and is promising as a drug which)Tj
T*
0.1488 Tw
[(increases gastric emptying, nausea and vomiting)]TJ
T*
0.01 Tc
-0.0519 Tw
(and gut transit time. ADL 9-2698, a new drug desi-)Tj
T*
0.0619 Tw
[(gned specifically for this purpose, is currently un-)]TJ
T*
0.0103 Tc
-0.0111 Tw
(der investigation.)Tj
/F3 1 Tf
9.5 0 0 9.5 301.896 242.855 Tm
0.0007 Tc
0 Tw
(Pimiennictwo)Tj
/F2 1 Tf
7.5 0 0 7.5 309.312 232.055 Tm
-0.0052 Tc
-0.075 Tw
[(1)-7.6(.)-379.6(Murphy D.B., Sutton J.A., Prescott L.F., Murphy M.B. Opio-)]TJ
1.2768 -1.3344 TD
-0.0001 Tc
-0.0658 Tw
[(id-induced delay in gastric emptying: a peripheral mecha-)]TJ
T*
-0.0002 Tc
-0.0019 Tw
(nism in humans. Anesthesiology 1997; 87 \(4\): 765770.)Tj
-1.2768 -1.3344 TD
0 Tc
-0.0475 Tw
[(2.)-374.4(Gue M., Fioramonti J., Junien J.L., Bueno L. Orally admini-)]TJ
1.2768 -1.3344 TD
-0.0002 Tc
-0.0316 Tw
(stered kappa but not mu opiate agonists enhance gastric)Tj
T*
0.0073 Tw
(emptying of a solid canned food meal in dogs. J. Pharm.)Tj
T*
0.0001 Tc
-0.0034 Tw
(Pharmacol. 1988; 40 \(12\): 873875.)Tj
-1.2768 -1.3344 TD
-0.0004 Tc
0.058 Tw
[(3.)-374.8(Dubois A. Endogenous opioids, gastric motility, and ga-)]TJ
1.2768 -1.3248 TD
-0.0002 Tc
-0.0725 Tw
(stric emptying. Gastroenterol. Clin. Biol. 1987; 11 \(3 cz)Tj
0 -1.3344 TD
-0.0001 Tc
0 Tw
(2\): 56B61B.)Tj
-1.2768 -1.3344 TD
0.0005 Tc
0.0818 Tw
[(4.)-373.9(Culpepper-Morgan J., Kreek M.J., Holt P.R., LaRoche D.,)]TJ
1.2768 -1.3344 TD
0 Tc
-0.0118 Tw
(Zhang J., OBryan L. Orally administered kappa as well as)Tj
T*
-0.0003 Tc
0.0533 Tw
(mu opiate agonists delay gastrointestinal transit time in)Tj
T*
-0.0002 Tc
-0.0017 Tw
(the guinea pig. Life Sci. 1988; 42 \(21\): 20732077.)Tj
-1.2768 -1.3344 TD
-0.0001 Tc
0.0283 Tw
[(5.)-374.5(Bouvier M., Kirschner G., Gonella J. Actions of morphine)]TJ
1.2768 -1.3344 TD
-0.0003 Tc
-0.0363 Tw
(and enkephalins on the internal anal sphincter of the cat:)Tj
T*
-0.0002 Tc
0.06 Tw
(relevance for the physiological role of opiates. J. Auton.)Tj
0 -1.3248 TD
0.0003 Tc
-0.0053 Tw
(Nerv. Syst. 1986; 16 \(3\): 219232.)Tj
9 0 0 9 76.464 734.255 Tm
-0.0201 Tc
0.1322 Tw
(Naltrekson \(NTX\) jest doustnie dziaajcym anta-)Tj
-1.568 -1.4 TD
-0.0199 Tc
-0.04 Tw
(gonist opioidowym stosowany w leczeniu zalenoci)Tj
T*
-0.0197 Tc
0.016 Tw
(od alkoholu i od narkotykw. Podobnie jak NLX, NTX)Tj
T*
0.17 Tw
(powoduje objawy odstawienia u pacjentw uzale-)Tj
T*
-0.0201 Tc
-0.0028 Tw
(nionych, ale take u osb cierpicych z powodu prze-)Tj
T*
-0.0199 Tc
0.0564 Tw
(wlekego widu [25]. Dawki, ktre spowoduj ust-)Tj
T*
-0.0311 Tc
-0.075 Tw
(pienie objaww ubocznych opioidw, mog by mniej-)Tj
T*
-0.0201 Tc
0.0648 Tw
(sze od dawek potrzebnych do odwrcenia analgezji.)Tj
T*
-0.0211 Tc
0.0555 Tw
(Brakuje bada dotyczcych )Tj
12.688 0 TD
-0.002 Tc
0 Tw
(przeczyszcz)Tj
5.392 0 TD
-0.021 Tc
0.0555 Tw
(ajcego dzia-)Tj
-18.08 -1.4 TD
-0.0198 Tc
-0.0492 Tw
(ania NTX. Antagonista ten nie wydaje si odpowiedni)Tj
T*
-0.0201 Tc
-0.0042 Tw
(do leczenia zapar spowodowanych opioidami.)Tj
1.568 -1.4 TD
-0.0248 Tc
-0.0176 Tw
(Pochodna NTX metylnaltrekson \(MTNTX\) jest)Tj
-1.568 -1.4 TD
-0.025 Tc
0.1028 Tw
(antagonist opioidowym znanym od dawna, ale do-)Tj
T*
-0.0297 Tc
-0.0743 Tw
[(tychczas lek ten nie mia wielkiego zastosowania w)-25.7(me-)]TJ
T*
-0.0253 Tc
-0.0704 Tw
[(dycynie. Obecnie rozwaa si jego wykorzystanie w)6.7()-29.3(ce-)]TJ
T*
-0.0326 Tc
-0.075 Tw
(lu zmniejszenia objaww ubocznych opioidw [26, 27].)Tj
T*
-0.0097 Tc
0.3255 Tw
(Dodanie grupy metylowej do NTX spowodowao)Tj
T*
-0.0251 Tc
-0.0595 Tw
(zmniejszenie lipofilnoci tego leku, co z kolei wywoao)Tj
T*
-0.0056 Tw
(zmniejszenie przechodzenia przez barier krew-mzg.)Tj
T*
-0.013 Tw
[(Zatem dziaanie MTNTX jest ograniczone do odwraca-)]TJ
T*
-0.0256 Tc
-0.075 Tw
(nia dziaania ubocznego opioidw na obwodzie. Natu-)Tj
T*
-0.009 Tw
(raln zalet tego leku jest brak interakcji z centralnymi)Tj
T*
-0.04 Tw
(receptorami opioidowymi i brak odwracania analgezji.)Tj
T*
-0.0254 Tc
0.0722 Tw
(Przeprowadzono ju kilka bada klinicznych dotycz-)Tj
T*
-0.0251 Tc
0 Tw
(cych tego leku, a inne wanie trwaj [28].)Tj
1.568 -1.4 TD
-0.0039 Tc
-0.074 Tw
(Metylnaltrekson powoduje odwrcenie dziaania)Tj
-1.568 -1.4 TD
0.0117 Tc
0.2259 Tw
(hamujcego oprnianie odka indukowanego)Tj
T*
-0.0003 Tc
0.0978 Tw
(przez opioidy [29]. W kontrolowanym, skrzyowa-)Tj
T*
-0.0002 Tc
0.0288 Tw
(nym badaniu obejmujcym 11 pacjentw podawa-)Tj
T*
-0.0001 Tc
-0.0049 Tw
(no na przemian albo morfin i placebo, albo morfi-)Tj
T*
-0.0002 Tc
-0.0277 Tw
(n i MTNTX. W grupie otrzymujcej morfin i place-)Tj
T*
0.0005 Tc
0.1138 Tw
(bo zaobserwowano znaczne op\012nienie oprnia-)Tj
T*
0.0001 Tc
-0.0011 Tw
(nia odka. Dodanie MTNTX spowodowao prawie)Tj
T*
-0.0125 Tc
-0.075 Tw
[(cakowite zniwelowanie dziaania morfiny \(p < 0,04\).)]TJ
T*
-0.0002 Tc
(Ponadto stwierdzono, e wchanianie paracetamolu)Tj
T*
0 Tc
0.0231 Tw
(u pacjentw, ktrym podawano morfin i placebo,)Tj
T*
0.0005 Tc
0.0643 Tw
(byo istotnie op\012nione w porwnaniu z grup le-)Tj
T*
-0.0003 Tc
-0.0445 Tw
[(czon morfin i MTNTX. Maksymalne stenia para-)]TJ
T*
0.0287 Tw
(cetamolu u chorych przyjmujcych morfin i place-)Tj
T*
-0.0002 Tc
-0.0016 Tw
(bo byy take znamiennie nisze \(p < 0,03\).)Tj
1.568 -1.4 TD
0.0149 Tc
0.4129 Tw
(W kontrolowanym badaniu opublikowanym)Tj
-1.568 -1.4 TD
-0.0002 Tc
0.2007 Tw
(przez Yuana i wsp. [30] 22 osobom, ktre przez)Tj
T*
-0.0006 Tc
0.0297 Tw
(duszy czas przyjmoway metadon w celu leczenia)Tj
T*
0.015 Tc
0.4611 Tw
(uzalenienia od narkotykw, podano doylnie)Tj
T*
0.0002 Tc
0.1 Tw
(MTNTX. W tym badaniu zastosowanie MTNTX po-)Tj
T*
0.0003 Tc
0.1407 Tw
(wodowao polepszenie oprniania odkowego,)Tj
T*
-0.0002 Tc
-0.0666 Tw
(zagodzenie nudnoci i wymiotw, a take przyspie-)Tj
T*
-0.0003 Tc
-0.0195 Tw
(szenie czasu pasau jama ustna-ktnica. U adnego)Tj
T*
-0.0023 Tw
(z badanych nie wystpiy objawy odstawienia.)Tj
1.568 -1.4 TD
0 Tc
0.22 Tw
(ADL 9-2698 jest nowym antagonist opioido-)Tj
-1.568 -1.4 TD
-0.004 Tc
-0.075 Tw
(wym dziaajcym jedynie na obwodzie. Oczekuje si,)Tj
T*
0.0002 Tc
0.0069 Tw
(e ten lek bdzie w stanie agodzi obwodowe nie-)Tj
T*
-0.0004 Tc
0.0648 Tw
(podane dziaania opioidw, w tym zaparcia. Ba-)Tj
T*
0 Tw
(dania kliniczne s w toku [31, 32].)Tj
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BT
/F1 1 Tf
7.5 0 0 7.5 62.34 771.0471 Tm
0 g
/GS2 gs
-0.0006 Tc
0.0067 Tw
(Polska Medycyna Paliatywna 2004, tom 3, nr 2)Tj
24.1248 -98.64 TD
-0.0001 Tc
0 Tw
(www.pmp.viamedica.pl)Tj
8.5 0 0 8.5 28.356 31.247 Tm
-0.0041 Tc
(170)Tj
/F3 1 Tf
11 0 0 11 62.34 730.0791 Tm
0.0003 Tc
(Wnioski)Tj
/F2 1 Tf
9 0 0 9 76.524 709.0551 Tm
-0.0006 Tc
0.2067 Tw
(By moe antagonici opioidowi dziaajcy na)Tj
-1.576 -1.4 TD
-0.0002 Tc
0.0334 Tw
(obwodzie stan si lekami, ktre, przynajmniej po-)Tj
T*
-0.0005 Tc
0.0666 Tw
(tencjalnie bd mogy zagodzi niektre dziaania)Tj
T*
0.0001 Tc
-0.0408 Tw
[(uboczne opioidw, w tym zaparcia. Doustnie poda-)]TJ
T*
-0.0005 Tc
0.0926 Tw
(ny NLX dziaa u niektrych osb przeczyszczajco,)Tj
T*
0.0001 Tc
0.0658 Tw
(ale take powoduje odwrcenie analgezji i nawrt)Tj
T*
-0.0004 Tc
0.0723 Tw
(blu. Naltrekson jest lekiem dziaajcym centralnie)Tj
T*
0.0004 Tc
0.0452 Tw
(iobwodowo, dlatego stosuje si go w leczeniu za-)Tj
T*
-0.0002 Tc
-0.0326 Tw
[(par. Natomiast jego pochodna MTNTX dziaa)]TJ
T*
0.0001 Tc
-0.0481 Tw
(jedynie obwodowo i jest obiecujcym lekiem powo-)Tj
T*
-0.0003 Tc
0.1019 Tw
(dujcym przyspieszenie oprniania odkowego,)Tj
T*
-0.0001 Tc
0.1462 Tw
(zagodzenie nudnoci i wymiotw, a take zago-)Tj
T*
-0.0004 Tc
0.0461 Tw
[(dzenie zaparcia. ADL 9-2698 to preparat, ktry zo-)]TJ
T*
-0.0005 Tc
0.0366 Tw
(sta specjalnie zsyntetyzowany, aby dziaa antago-)Tj
T*
-0.0001 Tc
-0.0389 Tw
(nistycznie jedynie na obwodzie, z pominiciem cen-)Tj
T*
0 Tc
-0.0056 Tw
(tralnych receptorw opioidowych. Badania z zasto-)Tj
T*
-0.0001 Tc
-0.0027 Tw
(sowaniem tego leku wanie trwaj.)Tj
7.5 0 0 7.5 69.756 458.855 Tm
0.1207 Tw
[(6.)-374.5(Moulin D.E., Iezzi A., Amireh R., Sharpe W.K., Boyd D.,)]TJ
1.2768 -1.3344 TD
0.0002 Tc
-0.055 Tw
(Merskey H. Randomised trial of oral morphine for chronic)Tj
T*
0.0001 Tc
-0.0023 Tw
(non-cancer pain. Lancet 1996; 347 \(8995\): 143147.)Tj
-1.2768 -1.3344 TD
-0.0003 Tc
-0.0076 Tw
[(7.)-374.7(Staats P.S., Markowitz J., Schein J. Incidence of constipa-)]TJ
1.2768 -1.3344 TD
-0.0005 Tc
0.0734 Tw
(tion associated with long-acting opioid therapy: a com-)Tj
T*
-0.0002 Tc
0 Tw
(parative study. South Med. J. 2004; 97 \(2\): 129134.)Tj
-1.2768 -1.3344 TD
0 Tc
0.0514 Tw
[(8.)-374.4(Portenoy R.K. Constipation in the cancer patient: causes)]TJ
1.2768 -1.3344 TD
0.0002 Tc
0.16 Tw
(and management. Med. Clin. North Am. 1987; 71 \(2\):)Tj
T*
0.0004 Tc
0 Tw
(303311.)Tj
-1.2768 -1.3248 TD
-0.0001 Tc
-0.0076 Tw
[(9.)-374.5(Sykes N.P. The relationship between opioid use and laxa-)]TJ
1.2768 -1.3344 TD
-0.0061 Tc
-0.0748 Tw
(tive use in terminally ill cancer patients. Palliat. Med. 1998;)Tj
T*
0.0002 Tc
-0.0033 Tw
(12 \(5\): 375382.)Tj
-1.8816 -1.3344 TD
0.1943 Tw
[(10.)-383.8(Sykes N.P. Current approaches to the management of)]TJ
1.8816 -1.3344 TD
-0.0002 Tc
0.0013 Tw
(constipation. Cancer Surv. 1994; 21: 137146.)Tj
-1.8816 -1.3344 TD
0.0017 Tw
[(11.)-384.2(Stewart J.J., Weisbrodt N.W., Burks T.F. Central and peri-)]TJ
1.8816 -1.3344 TD
-0.0003 Tc
0.0533 Tw
(pheral actions of morphine on intestinal transit. J. Phar-)Tj
T*
0.0001 Tc
-0.0011 Tw
(macol. Exp. Ther. 1978; 205 \(3\): 547555.)Tj
-1.8816 -1.3248 TD
-0.0002 Tc
-0.005 Tw
[(12.)-384.2(Manara L., Bianchetti A. The central and peripheral influ-)]TJ
1.8816 -1.3344 TD
-0.0051 Tc
-0.0752 Tw
(ences of opioids on gastrointestinal propulsion. Annu Rev.)Tj
T*
-0.0003 Tc
0.0017 Tw
(Pharmacol. Toxicol. 1985; 25: 249273.)Tj
-1.8816 -1.3344 TD
-0.0002 Tc
-0.0123 Tw
[(13.)-384.2(Stein C. Peripheral mechanisms of opioid analgesia. Ane-)]TJ
1.8816 -1.3344 TD
-0.0001 Tc
0.0014 Tw
(sth. Analg. 1993; 76 \(1\): 182191.)Tj
-1.8816 -1.3344 TD
0 Tc
-0.054 Tw
[(14.)-384(Radbruch L., Sabatowski R., Loick G., Kulbe C., Kasper M.,)]TJ
1.8816 -1.3344 TD
-0.0006 Tc
0.1689 Tw
(Grond S. i wsp. Constipation and the use of laxatives:)Tj
T*
-0.009 Tc
-0.0744 Tw
(acomparison between transdermal fentanyl and oral mor-)Tj
T*
-0.0002 Tc
-0.0011 Tw
(phine. Palliat. Med. 2000; 14 \(2\): 111119.)Tj
-1.8816 -1.3248 TD
0.0576 Tw
[(15.)-384.2(Fishman J., Roffwarg H., Hellman L. Disposition of nalo-)]TJ
1.8816 -1.3344 TD
0.1433 Tw
(xone-7,8,3H in normal and narcotic-dependent men. J.)Tj
T*
0.0001 Tc
-0.0022 Tw
(Pharmacol. Exp. Ther. 1973: 187 \(3\): 575580.)Tj
30.0576 74.2848 TD
-0.0004 Tc
0.1107 Tw
[(16.)-384.4(Fujimoto J.M. Isolation of naloxone-3-glucuronide from)]TJ
1.8816 -1.3248 TD
0 Tc
0.1274 Tw
(human urine. Proc. Soc. Exp. Biol. Med. 1970; 133 \(1\):)Tj
0 -1.3344 TD
0.0004 Tc
0 Tw
(317319.)Tj
-1.8816 -1.3344 TD
-0.0002 Tc
0.1667 Tw
[(17.)-384.2(Weinstein S.H., Pfeffer M., Schor J.M. Metabolism and)]TJ
1.8816 -1.3344 TD
-0.0089 Tc
-0.0747 Tw
(pharmacokinetics of naloxone. Adv. Biochem. Psychophar-)Tj
T*
0 Tc
-0.0016 Tw
(macol. 1973; 8 \(0\): 525535.)Tj
-1.8816 -1.3344 TD
-0.0004 Tc
-0.0288 Tw
[(18.)-384.4(Wahlstrom A., Winblad B., Bixo M., Rane A. Human brain)]TJ
1.8816 -1.3344 TD
0.1753 Tw
(metabolism of morphine and naloxone. Pain 1988; 35)Tj
T*
0.0004 Tc
-0.0066 Tw
(\(2\): 121127.)Tj
-1.8816 -1.3248 TD
-0.0003 Tc
0.1222 Tw
[(19.)-384.3(Sykes N.P. Oral naloxone in opioid-associated constipa-)]TJ
1.8816 -1.3344 TD
-0.0001 Tc
-0.0013 Tw
(tion. Lancet 1991; 337 \(8755\): 1475.)Tj
-1.8816 -1.3344 TD
-0.0249 Tc
-0.0628 Tw
[(2)-23.7(0)-23.7(.)-408.9(Culpepper-Morgan J.A., Inturrisi C.E., Portenoy R.K., Foley K.,)]TJ
1.8816 -1.3344 TD
-0.0003 Tc
-0.0583 Tw
(Houde R.W., Marsh F. i wsp. Treatment of opioid-induced)Tj
T*
-0.0006 Tc
-0.0183 Tw
(constipation with oral naloxone: a pilot study. Clin. Phar-)Tj
T*
0.0001 Tc
-0.004 Tw
(macol. Ther. 1992; 52 \(1\): 9095.)Tj
-1.8816 -1.3344 TD
0.1285 Tw
[(21.)-383.9(Latasch L., Zimmermann M., Eberhardt B., Jurna I. Tre-)]TJ
1.8816 -1.3344 TD
-0.0005 Tc
0.0077 Tw
(ament of morphine-induced constipation with oral nalo-)Tj
T*
-0.0002 Tc
0 Tw
(xone. Anaesthesist. 1997; 46 \(3\): 191194.)Tj
-1.8816 -1.3248 TD
-0.0148 Tc
-0.0703 Tw
[(2)-13.6(2)-13.6(.)-398.8(Meissner W., Schmidt U., Hartmann M., Kath R., Reinhart K.)]TJ
1.8816 -1.3344 TD
-0.0144 Tc
-0.0746 Tw
(Oral naloxone reverses opioid-associated constipation. Pain)Tj
T*
-0.0001 Tc
-0.0022 Tw
(2000; 84 \(1\): 105109.)Tj
-1.8816 -1.3344 TD
-0.0002 Tc
-0.0184 Tw
[(23.)-384.2(Sykes N.P. A volunteer model for the comparison of laxa-)]TJ
1.8816 -1.3344 TD
-0.0005 Tc
-0.0324 Tw
(tives in opioid-related constipation. J. Pain Symptom Ma-)Tj
T*
0 Tc
-0.0033 Tw
(nage. 1996; 11 \(6\): 363369.)Tj
-1.8816 -1.3344 TD
-0.0069 Tc
-0.075 Tw
[(2)-5.7(4)-5.7(.)-390.9(Liu M., Wittbrodt E. Low-dose oral naloxone reverses opio-)]TJ
1.8816 -1.3344 TD
-0.0005 Tc
0.0633 Tw
(id-induced constipation and analgesia. J. Pain Symptom)Tj
T*
0.0002 Tc
-0.005 Tw
(Manage. 2002; 23 \(1\): 4853.)Tj
-1.8816 -1.3248 TD
0.0198 Tc
0.2144 Tw
[(2)21(5)21(.)-364.2(Jones E.A., Dekker L.R. Florid opioid withdrawal-like)]TJ
1.8816 -1.3344 TD
0.0194 Tc
0.1534 Tw
[(reaction precipitated by naltrexone in a patient with)]TJ
T*
0.0201 Tc
0.22 Tw
(chronic cholestasis. Gastroenterology 2000; 118 \(2\):)Tj
T*
0.0209 Tc
0 Tw
(431432.)Tj
-1.8816 -1.3344 TD
0.0102 Tc
0.0467 Tw
[(2)11.4(6)11.4(.)-373.8(Rosow C.E. Methylnaltrexone: reversing the gastrointe-)]TJ
1.8816 -1.3344 TD
0.0097 Tc
0.1533 Tw
(stinal effects of opioids. Anesthesiology 1997; 87 \(4\):)Tj
T*
0.0113 Tc
0 Tw
(736737.)Tj
-1.8816 -1.3344 TD
0.0002 Tc
0.0156 Tw
[(27.)-383.8(Foss J.F., OConnor M.F., Yuan C.S., Murphy M., Moss J.,)]TJ
1.8816 -1.3344 TD
-0.0001 Tc
0.0409 Tw
(Roizen M.F. Safety and tolerance of methylnaltrexone in)Tj
0 -1.3248 TD
-0.0003 Tc
0.164 Tw
(healthy humans: a randomized, placebo-controlled, in-)Tj
0 -1.3344 TD
-0.0078 Tc
-0.0747 Tw
(travenous, ascending-dose, pharmacokinetic study. J. Clin.)Tj
T*
0.0002 Tc
-0.0033 Tw
(Pharmacol. 1997; 37 \(1\): 2530.)Tj
-1.8816 -1.3344 TD
-0.0001 Tc
-0.0275 Tw
[(28.)-384.1(De Ponti F. Methylnaltrexone progenics. Curr. Opin. Inve-)]TJ
1.8816 -1.3344 TD
0.0002 Tc
-0.0027 Tw
(stig. Drugs 2002; 3 \(4\): 614620.)Tj
-1.8816 -1.3344 TD
0.0199 Tc
0.1438 Tw
[(2)21.1(9)21.1(.)-364.1(Murphy D.B., Sutton J.A., Prescott L.F., Murphy M.B.)]TJ
1.8816 -1.3344 TD
0.0196 Tc
-0.0011 Tw
(Opioid-induced delay in gastric emptying: a peripheral)Tj
T*
0.0202 Tc
0.1655 Tw
[(mechanism in humans. Anesthesiology 1997; 87 \(4\):)]TJ
0 -1.3248 TD
0.0209 Tc
0 Tw
(765770.)Tj
-1.8816 -1.3344 TD
0.0001 Tc
0.0386 Tw
[(30.)-383.9(Yuan C.S., Foss J.F., OConnor M., Osinski J., Karrison T.,)]TJ
1.8816 -1.3344 TD
0 Tc
0.0216 Tw
(Moss J. i wsp. Methylnaltrexone for reversal of constipa-)Tj
T*
-0.0003 Tc
0.0792 Tw
(tion due to chronic methadone use: a randomized con-)Tj
T*
0 Tw
(trolled trial. JAMA 2000; 283 \(3\): 367372.)Tj
-1.8816 -1.3344 TD
0.0992 Tw
[(31.)-384.3(Schmidt W.K. Alvimopan* \(ADL 8-2698\) is a novel peri-)]TJ
1.8816 -1.3344 TD
0.2241 Tw
[(pheral opioid antagonist. Am. J. Surg. 2001; 182 \(5A)]TJ
T*
0.0067 Tw
(supl.\): 27S38S.)Tj
-1.8816 -1.3344 TD
0 Tc
0.0572 Tw
[(32.)-384(Liu S.S., Hodgson P.S., Carpenter R.L., Fricke J.R. Jr. ADL)]TJ
1.8816 -1.3248 TD
-0.0002 Tc
0.0133 Tw
(8-2698, a trans-3,4-dimethyl-4-\(3-hydroxyphenyl\) piperi-)Tj
0 -1.3344 TD
-0.004 Tc
-0.0744 Tw
(dine, prevents gastrointestinal effects of intravenous mor-)Tj
T*
-0.0002 Tc
-0.01 Tw
(phine without affecting analgesia. Clin. Pharmacol. Ther.)Tj
T*
-0.0001 Tc
-0.0022 Tw
(2001; 69 \(1\): 6671.)Tj
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0 J 0 j 0.216 w 10 M []0 d
1 i
62.34 478.187 m
279.204 478.187 l
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